ABSTRACT
Exposure of rats to nitrobenzene produces a degeneration of the seminiferous epithelium of the testes. Sperm production was continuously monitored in rats surgically prepared by anastomosing the vas deferentia with the urinary bladder to evaluate the reversibility of nitrobenzene toxicity. Rates of sperm production were monitored by collecting urine and counting sperm microscopically with a hemocytometer. Six weeks after surgery, rats were dosed p.o. with a single dose of 300 mg/kg of nitrobenzene in corn oil. Sperm were not detected in the urine of treated rats between 32 and 48 days after treatment. Despite the fact that degenerative changes in the seminiferous tubules were observed histologically as early as 3 days after dosing, there was a 32-day lag period between treatment and cessation of sperm output in treated rats. Histological examination showed that pachytene spermatocytes and step 1-2 spermatids were the most susceptible cell stages to nitrobenzene and were observed forming into giant cells as early as 3 days after treatment. However, repair was substantial by 3 weeks after treatment and by days 76-100, the rate of sperm output reached 78% of the control group. By 100 days after treatment, there was greater than 90% regeneration of the seminiferous epithelium. Thus, a single oral dose of nitrobenzene induced testicular degeneration and approximately a 17-day period of aspermia resulted. Back-dating of the aspermic period to the timing of the spermatogenic cycle closely corresponded with the same germ cell stages that were observed degenerating in histologic examinations. Thus, changes in sperm output from vasocystotomized rats correlated well with histopathologic changes, demonstrating the value of this technique for toxicity studies.
Subject(s)
Nitrobenzenes/adverse effects , Spermatogenesis/drug effects , Administration, Oral , Animals , Male , Rats , Rats, Inbred F344 , Regeneration , Seminiferous Tubules/drug effects , Sperm Count/drug effects , Urinary Bladder/surgery , Vas Deferens/surgeryABSTRACT
1,6-Dinitropyrene (DNP) was found to be an extremely potent genotoxicant in metabolically competent primary cultures of human and rat hepatocytes. Dose-dependent increases in DNA repair as measured by unscheduled DNA synthesis (UDS) were observed in the range from 0.05 to 5 microM 1,6-DNP for both species, indicating that the rat-hepatocyte assay is an appropriate model for assessing genotoxic potential in human hepatocytes for this class of compound. Unlike some nitroaromatic compounds, 1,6-DNP did not require gut flora for metabolic activation. No DNA repair was observed in hepatocytes isolated from rats treated with 50 mg/kg 1,6-DNP in corn oil by gavage 2, 12 or 24 h previously. The reason for the lack of a response in vivo is not known, but may relate to detoxification or distribution of the compound in the animal.
